Anti-PM/Scl
antibodies represent a specific serological marker for a subset of patients with scleroderma (Scl) and
polymyositis (PM), and especially with the PM/Scl overlap syndrome (PM/Scl). Anti-PM/Scl reactivity is found in 24% of PM/Scl patients and is found in 3-10% of Scl and PM patients. The PM/Scl
autoantigen complex comprises 11-16 different
polypeptides. Many of those
proteins can serve as targets of the anti-PM/Scl B-cell response, but most frequently the PM/Scl-100 and PM/Scl-75
polypeptides are targeted. In the present study we investigated the clinical relevance of a major alpha helical PM/Scl-100
epitope (PM1-alpha) using a newly developed
peptide-based immunoassay and compared the immunological properties of this
peptide with native and recombinant PM/Scl
antigens. In a technical comparison, we showed that an ELISA based on the PM1-alpha
peptide is more sensitive than common techniques to detect anti-PM/Scl
antibodies such as immunoblot, indirect immunofluorescence on HEp-2 cells and ELISA with recombinant PM/Scl
polypeptides. We found no statistical evidence of a positive association between anti-PM1-alpha and other
antibodies, with the exception of known PM/Scl components. In our cohort a negative correlation could be found with anti-Scl-70 (
topoisomerase I), anti-Jo-1 (
histidyl tRNA synthetase) and anti-centromere
proteins. In a multicenter evaluation we demonstrated that the PM1-alpha
peptide represents a sensitive and reliable substrate for the detection of a subclass of anti-PM/Scl
antibodies. In total, 22/40 (55%) PM/Scl patients, 27/205 (13.2%) Scl patients and 3/40 (7.5%) PM patients, but only 5/288 (1.7%) unrelated controls, tested positive for the anti-PM1-alpha
peptide antibodies. These data indicate that anti-PM1-alpha
antibodies appear to be exclusively present in sera from PM/Scl patients, from Scl patients and, to a lesser extent, from PM patients. The anti-PM1-alpha ELISA thus offers a new serological marker to diagnose and discriminate different systemic autoimmune disorders.